Endothelial prolyl hydroxylase 2 is necessary for Angiotensin II-mediated renal fibrosis and injury.

Endothelial prolyl hydroxylase 2 is necessary for Angiotensin II-mediated renal fibrosis and injury. Am J Physiol Renal Physiol. 2020 Jul 27;: Authors: Zhao Y, Zeng H, Liu B, He X, Chen JX Abstract Angiotensin II (Ang II) is the key contributor to renal fibrosis and injury. The present study is to investigate the role of endothelium prolyl hydroxylase 2 (PHD2) in Ang II-mediated renal fibrosis and injury. In vitro, endothelial cells (ECs) were isolated from PHD2f/f control (wild type, WT) mice or PHD2 EC knockout (PHD2ECKO) mice. In vivo, WT and PHD2ECKO mice were infused with Ang II (1000ng/kg/min) for 28 days. Renal fibrosis, reactive oxygen species (ROS) and iron contents were measured. Knockout of PHD2 resulted in a significant increase in expression of HIF-1 and HIF-2 in ECs. Intriguingly, knockout of PHD2 significantly reduced the expression of Ang II type 1 receptor (AT1R) in the ECs. WT mice infused with Ang II caused increases in renal fibrosis, ROS formation and iron contents. Ang II treatment led to a downregulation of PHD1 expression and upregulation of HIF-1α and HIF-2α in the renal cortex and medulla. Knockout of PHD2 in EC blunted Ang II-induced downregulation of PHD1 expression. Furthermore, knockout of PHD2 in EC attenuated Ang II-induced the expression of HIF-1α, HIF-2α, transforming growth factor-β1 (TGF-β1), p47phox and gp91phox, heme oxygenase-1 (HO-1), ferroportin. This was accompanied by a significa...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research